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Indian Pediatr 2011;48: 406-407 |
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Reversal of Severe Wilson Arthropathy by Liver
Transplantation |
Aabha Nagral and Kiran Sathe
Consultant Hepatologist, Pediatric Liver Clinic,
Department of Gastroenterology, and Department of Pediatrics,
Jaslok Hospital & Research Centre, Mumbai, India.
Correspondence to: Dr Aabha Nagral, Consultant
Hepatologist, 7, Snehasagar, Prabhanagar,
Prabhadevi, Mumbai 400 025, India.
Email: [email protected]
Received: December 8, 2009;
Initial review: January 11, 2010;
Accepted: February 22, 2010.
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Wilson disease is associated with multisystem involvement. We describe a
patient of Wilson disease with severe arthropathy, which completely
reversed following liver transplantation. This is the first case report
in literature describing the complete reversal of Wilson disease related
arthropathy by liver transplantation.
Key words: Arthropathy, Children, Copper, d-penicillamine,
Wilson disease.
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An 11-year-old boy presented
with episodes of recurrent jaundice of two years duration. On
investigations he was diagnosed to have Wilson disease (low serum
ceruloplasmin, high urine copper, slit lamp showing KF rings and
sunflower cataracts). He had no neurological symptoms. He had a
serum bilirubin of 3.5 mg/dL (direct 2 mg/ dL), AST-104 IU/L, ALT -
205 IU/L, ALP - 160 IU/L, serum albumin - 2.9 g/dL, INR - 1.8, Hb –
10.8g /dL, WBC – 4800/cmm , platelets – 88,000/cmm. USG of the
abdomen showed a cirrhotic liver with portal hypertension and free
fluid in peritoneal cavity. He was initially treated with d-penicillamine.
He was fairly well compensated for about one and half years while on
d-penicillamine. However, his white cell count and platelet counts
progressively decreased (lowest WBC count was 2100/cmm and platelet
count of 35,000/cmm) and this was attributed to a combination of
hypersplenism and d-penicillamine and he was switched to trientine.
After two months, his liver decompensated after an episode of fever
and spontaneous bacterial peritonitis. He had a rising bilirubin and
grade two hepatic encephalopathy with a deteriorating coagulation
profile. He developed progressively increasing joint involve-ment,
which started a month after the episode of encephalopathy.
The joint pains involved both large and small
joints (knees, ankles with small joints of the fingers and toes).
The involvement was symmetrical, with tenderness and restricted
joint mobility with swelling of the knee joints, which seemed to be
predominantly involved. The joint pains severely affected his
activities of daily living including sleep He was investigated for
the arthropathy - anti nuclear antibody, rheumatoid factor, direct
coomb’s test, chikungunya IgM antibody, and HLA B27- were negative;
serum uric acid was 1.8 mg/dL (2.5-7.8 mg/dL) and anti streptolysin
O showed a normal value of less than 200 Todd units.
X-ray of the knee joints revealed
periarticular soft tissue swelling and osteopenic bones. Ultrasound
of the knee joints revealed bilateral effusions of the suprapatellar
bursae. MRI of the brain did not show any evidence of copper
deposition. Since no other cause of joint pain was found, a
diagnosis of Wilson’s arthropathy was made. He was treated with
paracetamol and opiate based drugs for the joint pains and local
fomentations, which provided minimal relief.
Subsequently, he underwent a living related right
lobe liver transplantation (donor being his mother) after 2 months
of decompensation (in the form of fever, SBP and hepatic
encephalopathy). At the time of transplantation, his PELD (Pediatric
end stage liver disease) score was 36 and the liver profile at the
time of liver transplantation revealed AST – 305 mg/dL, ALT–290 mg/dL,
GGTP–275 mg/dL, total bilirubin – 20.4 mg/dL, direct bilirubin –
14.3 mg/dL, INR – 3.4, serum creatinine – 0.4mg/dL, serum albumin –
2.5mg/dL. He was initially on tacrolimus and steroid based
immunosuppressive therapy and later switched to cyclosporine due to
tacrolimus related toxicity.
The joint problem showed remarkable improvement,
with complete disappearance of the pain and joint swellings as soon
as he was mobilized by the fourth day post transplantation. He is
now one and half years post transplantation and has no joint pains,
with a normal liver profile and leading a normal life.
Discussion
Our patient presented as an established case of
Wilson disease with primary liver involvement and development of
symmetric polyarthropathy. He had been treated with d-penicillamine
for one and a half years. However, the arthropathy started after
discontinuation of the drug thereby ruling out d-penicillamine
induced arthropathy. Unlike Wilson disease related arthropathy,
which is a chronic joint damage, penicillamine induced arthropathy
is an acute problem, which subsides on stopping the drug or
decreasing its dose. It is in fact a manifestation of delayed
hypersensitivity reaction in response to d-penicillamine [1].
The possibility of juvenile idiopathic arthritis was not considered
since a minimum duration of 6-12 weeks of joint pains is an
essential criteria for its diagnosis [2]. This was not the case in
our patient. We also ruled out other causes of arthropathy.
The arthropathy of Wilson disease is usually a
late occurrence in the course of the disease process, frequently
occurring after 20 years of age although it could be the initial
presenting feature of the disease. It occurred two years after the
onset of liver symptoms in our patient. Symptomatic joint disease
occurs in 25-50% of such patients. The joint pathology is a
degenerative process resembling premature osteoarthritis in addition
to generalized osteopenia [3]. Synovial copper deposition has been
postulated as the likely explanation for the occurrence of
arthropathy [3,4]. Wilson disease related arthropathy has been
described more often in patients who had become neurologically
disabled [5]. In our patient, there was no evidence of neurological
involvement either clinically or on imaging. It was unlikely that
the joint pains responded to steroids, as there was no evidence of
other etiologies (SLE or Juvenile idiopathic arthritis) on workup,
which would respond to steroids.
Acknowledgment: Dr Raju Khubchandani.
Contributors: AN conceptualized and edited
the paper. KS wrote the initial manuscript. Both authors approved
the final manuscript.
Funding: None.
Competing interests: None stated.
References
1. Walshe JM, Golding DN. Penicillamine inducted
arthropathy in Wilson’s Disease. Proc Roy Soc.1977; 70:4-6.
2. Hay WW, Levin MJ, Sondheimer MJ. Rheumatic
diseases. In: Soep J. Mollister JR. Current Diagnosis and
Treatment- Pediatrics. 19th Edition. Denver: Lange Publication;
2009. p.798.
3. Misra AK, Biswas A, Ganguly G. Arthropathic
presentation of Wilson’s disease. J Assoc Physicians India.
2004;52:246-8.
4. Menery KA, Elder W, Brewer GJ, Braunstein EM,
Schumacher HR, Fox IH. The arthropathy of Wilson’s disease; clinical
and pathologic features J Rheumatol. 1988;15:33.
5. Stracciari A, Tempestini A, Borghi A, Guarino
M. Effect of liver transplantation on neurological manifestations in
Wilson disease. Arch Neurol. 2000;57:384-6.
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